HMGB1-mediated pyroptosis promotes inflammation and contributes to skeletal muscle atrophy induced by cigarette smoke

This study reveals that the levels of High-mobility group box 1 (HMGB1) protein in patients with chronic obstructive pulmonary disease (COPD) are significantly higher than in healthy nonsmoking individuals and are negatively correlated with the degree of skeletal muscle atrophy. Through in vivo and in vitro experiments, we have confirmed that HMGB1 promotes inflammatory responses through the HMGB1/TLR4-NLRP3-GSDMD-Caspase-1-mediated pyroptosis pathway, thereby exacerbating muscle wasting. This pathway represents a potential novel therapeutic target for the treatment of skeletal muscle atrophy.